| Author, Year | Aims | Time Period Covered | Eligibility Criteria | Number of Patients | Characteristics of Identified Articles: Study Designs | Characteristics of Identified Articles: Populations | Characteristics of Identified Articles: Interventions | Main Results | Subgroups |
|---|---|---|---|---|---|---|---|---|---|
| Bjordal, 2007197 | To determine the short-term pain-relieving effects of seven pharmacological agents for OA knee pain | MEDLINE, Embase, PedRo, Cochrane Controlled Trials Register 1996 through November 2005 | Diagnosis: Knee OA verified by clinical exam and/or by x ray. If less than 4 trials available for an intervention, trials also including hip OA were considered, if more than 2/3 of their patients had knee OA; Symptom duration: 3 months; Trial designs: Blinded, placebo-controlled parallel groups RCTs; Outcome measures: Pain intensity within 4 weeks of treatment start on WOMAC or on a 100mm VAS for global or walking pain. Pain intensity at 8–12 weeks follow-up; Intervention groups: Identical placebo drug and adequate daily defined drug dosage equal to or exceeding set dosages per drug: paracetamol 4g, diclofenac 100mg, etodolac 400mg, ibuprofen 2400 mg, nabumetone 1500mg, naproxen 1000mg, oxaprozin 1200mg, tiaprofenic acid 600mg, valdecoxib 10mg, celecoxib 200mg, meloxicam 7.5mg, etoricoxib 30mg, lumiracoxib 200mg, rofecoxib 12.5mg, topical diclofenac, piroxicam or meloxicam 1%, ibuprofen gel 3%, triamcinolone 20mg, methylprednisolone 40mg, cortivazol 3.75mg, glucosamine sulfate 1500mg, chondroitin sulfate 800mg, codeine 50mg, oxymorphone 20mg, oxycodone 20mg, morphine sulfate 30mg, tramadol 100mg | 14,060 patients for all included drugs. 9964 patients received Oral NSAIDs including coxibs, 749 received topical NSAIDs, 401 received glucosamine sulfate, 362 received chondroitin sulfate | 64 RCTs total. 25 RCTs of oral NSAIDs (including coxibs), 9 topical NSAIDs, 7 glucosamine sulfate, 6 chondroitin sulfate | Mean Age: Oral NSAIDs: 62.6 years Topical NSAIDs: 64.2 years Glucosamine sulfate: 58.6 years Chondroitin sulfate: 63.0 years Mean baseline pain on 100mm VAS: Oral NSAIDs: 64.3 Topical NSAIDs: 54.7 Glucosamine sulfate: 57.8 Chondroitin sulfate: 50.7 | Trials of included Oral NSAIDs:* 6 celecoxib studies; 2 naproxen studies; 2 diclofenac studies; 3 etodolac studies; 1 diflunisal study; 1 meloxicam study; 2 nabumetone studies; 1 oxaprozin study Trials of included Topical NSAIDs: 7 diclofenac, 2 eltenac, 1 ibuprofen Trials of glucosamine: 7 Trials of chondroitin: 6 | Best mean difference of change over placebo (100mm VAS): Glucosamine: 4.7 (95% CI 0.3 to 9.1) Chondroitin: 3.7 (95% CI 0.3 to 7.0) Glucosamine and chondroitin did not have effect size or 95% CI exceeding the mean threshold for minimal clinical important improvement, slight improvement, or minimal perceptible improvement | NR |
| Hochberg, 2010199 | To update the 2008 systematic review and meta-analysis with results of an updated meta-analysis that includes data from two recently published studies and limits the pooling to studies of 2- year duration | 1996–October 2007 | RCTs of 2-year duration that compared orally administered chondroitin sulfate to placebo and reported structural outcomes in the form of change in minimum joint space. No language restriction was applied. | 1179 | Randomized controlled trials | Michel et al., 2005: mean age 63, 52% women Sawitzke et al., 2008: mean age 57, 68% women Kahan et al., 2009: mean age 62, 68% women | Michel et al., 2005: 800 mg chondroitin sulfate once daily, 24 month duration Sawitzke et al., 2008: 400 mg chondroitin sulfate three times daily, 24 month duration Kahan et al., 2009: 800 mg chondroitin sulfate once daily, 24 month duration | Joint space narrowing (mm ± SD): Michel et al., 2005: CS: −0.045 ± 0.48, PBO: 0.07 ± 0.56; Mean difference (mm (95% CI)): 0.12 (0.00 to 0.23); Effect size (95 % CI): 0.22 (0.01 to 0.45) Sawitzke et al., 2008: CS: 0.107 ± 0.68, PBO: 0.166 ± 0.68; Mean difference (mm (95% CI)): 0.06 (−0.17 to 0.28); Effect size (95% CI): 0.09 (−0.24 to 0.42) Kahan et al., 2009: CS: 0.07 ± 0.03, PBO: 0.31 ± 0.04; Mean difference (mm (95% CI)): 0.14 (0.06 to 0.21); Effect size (95% CI): 0.26 (0.11 to 0.42) Pooled analysis: Mean difference (mm (95% CI)): 0.13 (0.06 to 0.19); Effect size (95% CI): 0.23 (0.11 to 0.35) | NR |
| Lee, 2010200 | To assess the structural efficacies of daily glucosamine sulfate and chondroitin sulfate in patients with knee OA | Through July 2008 | English language RCTs that compared glucosamine sulfate or chondroitin sulfate with a placebo in patients with OA, and utilized JSN as an outcome variable after treatment commencement. Studies were excluded if they did not contain a placebo group, if the OA site was not the knee joint, they did not contain adequate data, or if they were cross-sectional. | 749 | Randomized controlled trials | Pavelka et al, 2002: mean age patients: 61.2, controls: 63.5; 79% female patients, 76% female controls Reginster et al, 2001: mean age patients: 66.0, controls: 65.5; 75% female patients, 78% female controls Kahan et al, 2006: mean age not available; 68% female patients, 68% female controls Michel et al, 2005: mean age patients: 62.5, controls: 63.1; 51% female patients, 52% female controls Uebelhart et al, 2004: mean age patients: 63.2, controls: 63.7; 79.6% female patients, 82.1% female controls Uebelhart et al, 1998: mean age patients: 60.13, controls: 57.11; 47.8% female patients, 56.5% female controls | Pavelka et al, 2002: GS 1,500 mg qd Reginster et al, 2001: GS 1,500 mg qd Kahan et al, 2006: CS 800 mg qd Michel et al, 2005: CS 800 mg qd Uebelhart et al, 2004: CS 800 mg 2 periods of 3 months during 1 year Uebelhart et al, 1998: CS 400 bid | Glucosamine Sulfate: std diff in means (95% CI): Follow-up for 1 year (2 studies): 0.078 (−0.116 to 0.273), p=0.429 Follow- up for 3 years (2 studies): 0.432 (0.235 to 0.628), p=0.000 JSN > 0.5 mm (2 studies): OR 0.361 (0.204–0.640), p=0.000 Chondroitin Sulfate: std diff in means (95% CI): Minimum JSW (3 studies): 0.317 (0.136–0.497), p=0.001 Mean JSW (4 studies): 0.236 (0.148–0.386), p=0.000 Follow- up for 1 year (2 studies): 0.295 (0.000–0.590), p=0.050 Follow- up for 2 years (2 studies): 0.261 (0.131–0.392), p=0.000 | NR |
| Vlad, 2007201 | To identify factors that explain heterogeneity in trials of glucosamine | 1966–2006 | Randomized, double-lind, placebo- controlled trials of parenteral or oral glucosmine for pain from OA of the knee or hip, and subjects were followed for >4 weeks. | 2613 | Randomized controlled trials | Mean age, % female NR | Glucosamine preparation: Clegg et al, 2006: Hydrochloride Herrero- Beaumont et al, 2005: GS Usha and Naidu, 2004: GS McAlindon et al 2004: Hydrochloride and GS Cibere et al, 2004: GS Pevelka et al, 2002: GS Hughes and Carr, 2002: GS Reginster et al, 2001: GS Rindone et al, 2000: GS Houpt et al, 1999: Hydrochloride Reichelt et al, 1994: GS Noack et al, 1994: GS Vajaradul, 1981: GS Pujalte et al, 1980: GS Rovati et al, 1999: GS | Pooled estimates of heterogeneity and pooled effect estimates (95% CI), P for difference: All studies (15 studies): 0.35 (0.14, 0.56) Glucosamine hydrochloride (3 studies): 0.06 (−0.08, 0.20) Glucosamine sulfate (12 studies): 0.44 (0.18, 0.70) Industry funding absent (4 studies): 0.05 (−0.32, 0.41) Industry funding present (11 studies): 0.47 (0.24, 0.70), p=0.05 Industry participation absent (7 studies): 0.11 (−0.16, 0.38) Industry participation present (8 studies): 0.55 (0.27, 0.84), p=0.02 Industry-affiliated author absent (8 studies): 0.16 (−0.11, 0.42) Industry-affiliated author present (7 studies): 0.55 (0.27, 0.84), p=0.04 Rottapharm product absent (7 studies): 0.11 (−0.16, 0.38) Rottapharm product present (8 studies): 0.55 (0.29, 0.82), p=0.01 Allocation concealment adequate (5 studies): 0.09 (−0.24,0.42) intermediate (6 studiess): 0.47 (0.14, 0.80) inadequate (4 studies): 0.54 (0.14, 0.94), p=0.09 No ITT analysis (5 studies): 0.44 (0.03, 0.84) ITT analysis (10 studies): 0.31 (0.05, 0.58), p=0.62 Jadad score 1–3 (4 studies): 0.30 (−0.14, 0.73) Jadad score 4–5 (11 studies): 0.37 (0.11, 0.63) No rescue medication (3 studies): 0.55 (0.01, 1.10) Rescue medication use (12 studies): 0.31 (0.07, 0.55), p=0.42 | NR |
| Wandel, 2010198 | To determine the clinical effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in OA of the hip or knee | MEDLINE, EMBASE, CINAHL, and Cochrane Controlled Trials Register through June 2010. | Randomized trials with an average of at least 100 patients with knee or hip osteoarthritis per arm. Comparisons included chondroitin sulphate, glucosamine sulphate, glucosamine hydrochloride, or the combination of any two with placebo or head to head. Excluded trial arms with sub-therapeutic doses (<800mg/day of chondroitin, <1500mg/day glucosamine. | 3803 to the interventions or placebo. Glucosamine sulphate vs. Placebo: 5 trials, 1104 randomized patients; Glucosamine sulphate or hydrochloride vs. Placebo: 1 trial, 205 patients; Chondroitin sulphate vs. Placebo: 3 trials 1229 patients; Glucosamine hydrochloride, chondroitin sulphate, and their combination vs. placebo: 1 trial, 1265 patients | 10 RCTs: designs not specified | 8 trials with knee OA only, one trial with hip or knee OA, one trial with hip OA only. Mean age: 58–66 years % Female: 27–86 (median = 68%) Average duration of symptoms: 6 months–10 years | 6 glucosamine vs. placebo 3 chondroitin vs. placebo 1 glucosamine, chondroitin, combination vs. placebo | Pain Intensity (10cm VAS): Glucosamine vs. Placebo: −0.4 cm (−0.7 to −0.1) Chondroitin vs. Placebo: −0.3 cm (−0.7 to 0.0) Glucosamine and Chondroitin vs. Placebo: −0.5 cm (−0.9 to 0.0) Radiological joint space difference (negative number favors intervention): Glucosamine vs. Placebo: −0.2 mm (−0.3 to 0.0) Chondroitin vs. Placebo: −0.1mm (−0.3 to 0.1) Glucosamine and Chondroitin vs. Placebo: 0.00 mm (−0.2 to 0.2) Adverse Events, OR (95% CI): Glucosamine vs. Placebo: 0.94 (0.59 to 1.47) Chondroitin vs. Placebo: 0.99 (0.49 to 2.00) Glucosamine and Chondroitin vs. Placebo: no data Withdrawals due to AE, OR (95% CI) Glucosamine vs. Placebo: 0.99 (0.61 to 1.50) Chondroitin vs. Placebo: 0.92 (0.56 to 1.51) Glucosamine and Chondroitin vs. Placebo: 0.90 (0.43 to 1.85) | Estimated differences in pain intensity between supplements and placebo were on average 0.5 cm (0.1 to 0.9) higher in industry sponsored trials (p=0.02 for interaction) |
AE = adverse event; CI = confidence interval; CS = chondroitin sulfate; ITT = intention to treat; GS = glucosamine sulfate; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OR = odds ratio; RCT = randomized controlled trial; VAS = visual analogue scale; WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index
Characteristics of oral NSAID trials of included drugs for the current systematic review.
From: Appendix I, Evidence Tables: Glucosamine and Chondroitin Studies
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